Potential for interferon-alpha-based therapy in mesothelioma: assessment in a murine model.

Abstract

Malignant mesothelioma is an aggressive tumor, usually induced by asbestos exposure, that has a poor prognosis and is unresponsive to conventional therapy. The present study was aimed at assessing the potential for interferon-alpha (IFN-alpha)-based therapies in a murine model for malignant mesothelioma. The effect of recombinant human IFN-alpha B/D on tumor growth, alone and in combination with either of two immunomodulatory and antiproliferative agents beta-carotene or alpha-difluoromethylornithine (DFMO), was assessed. The data suggest that IFN-alpha treatment is most efficacious when commenced early in tumor development. Combination of IFN-alpha with either DFMO or dietary beta-carotene supplementation improved the effect of an otherwise suboptimal IFN-alpha therapy regimen. Both IFN-alpha and beta-carotene had in vivo stimulatory effects on immune cells, perhaps indirectly by inhibiting TGF-beta generation. The immunomodulatory effects may contribute, at least in part, to the positive antitumor and clinical activities of the treatments in this model.

• Authors: H Bielefeldt-Ohmann, D R Fitzpatrick, A L Marzo, A G Jarnicki, A W Musk, B W Robinson
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 15 Issue 3 Pg. 213-23 (Mar 1995) ISSN: 1079-9907 [Print] United States
• PMID: 7584666 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Interferon Type I
• RNA, Messenger
• Recombinant Proteins
• Transforming Growth Factor beta
• beta Carotene
• Carotenoids
• Eflornithine

Topics

• Adjuvants, Immunologic (therapeutic use)
• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carotenoids (administration & dosage, therapeutic use)
• Eflornithine (administration & dosage, therapeutic use)
• Female
• Interferon Type I (administration & dosage, therapeutic use)
• Lymphocytes, Tumor-Infiltrating (drug effects, immunology)
• Macrophages (drug effects, immunology)
• Mesothelioma (genetics, immunology, therapy)
• Mice
• Mice, Inbred CBA
• Mice, Inbred Strains
• RNA, Messenger (biosynthesis)
• Recombinant Proteins
• Transforming Growth Factor beta (metabolism)
• Tumor Cells, Cultured
• beta Carotene